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Title: Modelling of metabolism of praziquantel by isolated enzymes, whole cells and genetically modified cells

Abstract:

Knowledge about metabolism of drugs or molecules, that would be pharmaceuticals, 1s very important and useful to bring substances into health care. In the experimental part metabolism of praziquantel (PZQ), a highly lipophilic drug, that is almost insoluble in water, was studied. The metabolism of PZQ was investigated by using in vitro models of biotransformations, applying microbiological native or genetically, modified systems. Native cells of Saccharomyces ellipsoideus and Cunninghamella echinulata were used. Using C. echinulata for biotransformation 3 metabolites of PZQ were obtained and identified. To create more efficient and favourable system to examine PZQ metabolism computer simulation by different programs was performed. According to these simulations isoforms of cytochrome P-450, that play a very important role in PZQ biotransformations were selected, namely: isoenzyme 3A4 and 2B6. In the next step humane cytochrome P450 3A4 and 2B6 were cloned and expressed in Escherichia coli DH5a and Saccharomyces cerevisiae W(R) respectively. For biotransformations of PZQ whole cells of modified microorganisms, broken cells of modified microorganisms, and selected fractions of broken cells were used. In all experiments hydroxylated derivatives of PZQ were obtained. We can clearly state, that the metabolism of PZQ was conducted in the created systems. ; Additionally, the eukaryotic systems in biotransformations of PZQ were more efficient and could provide useful model to examine metabolism of different substances, that would be a potential drugs.

Place of publishing:

Kraków

Level of degree:

2 - studia doktoranckie

Degree discipline:

biologia molekularna ; farmacja

Degree grantor:

Wydział Farmaceutyczny

Promoter:

Kieć-Kononowicz, Katarzyna

Date issued:

2008

Identifier:

oai:dl.cm-uj.krakow.pl:1041

Call number:

ZB-108004

Language:

pol

Access rights:

tylko w bibliotece

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Last modified:

Jul 21, 2022

In our library since:

Nov 21, 2012

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36

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0

All available object's versions:

http://dl.cm-uj.krakow.pl:8080/publication/1041

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ZB-108004 Jul 21, 2022
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